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The VEGF pathway in cancer and disease: responses, resistance, and the path forward

Mark W Kieran1, Raghu Kalluri, Yoon-Jae Cho

  • 1Department of Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. mark_kieran@dfci.harvard.edu

Cold Spring Harbor Perspectives in Medicine
|December 5, 2012
PubMed

Insights

Targeting cancer neovascularization with anti-angiogenesis therapies, particularly anti-vascular endothelial growth factor (VEGF) approaches, shows promise. However, resistance mechanisms and toxicity limit their effectiveness as monotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Antiangiogenesis, targeting tumor blood vessel formation, emerged as a cancer treatment strategy 40 years ago.
  • Vascular Endothelial Growth Factor (VEGF) is a key cytokine in tumor neovascularization and inflammatory diseases.
  • Significant progress has been made in identifying angiogenic factors, their targets, signaling pathways, and inhibitors.

Purpose of the Study:

  • To review the fundamental biology of VEGF and its receptors.
  • To examine the clinical applications of anti-VEGF therapies in various diseases.
  • To discuss the toxicity profiles and resistance mechanisms associated with anti-VEGF agents.

Main Methods:

  • Literature review of scientific publications on VEGF and antiangiogenesis.
  • Analysis of clinical trial data and therapeutic outcomes.
  • Examination of preclinical studies on resistance mechanisms.

Main Results:

  • VEGF plays a central role in cancer and inflammatory disease neovascularization.
  • Anti-VEGF therapies have been developed and utilized in clinical settings.
  • Toxicity and resistance mechanisms have been identified as significant challenges for monotherapy.

Conclusions:

  • Understanding VEGF biology is crucial for developing effective cancer therapies.
  • Anti-VEGF strategies offer therapeutic potential but require careful management of toxicity and resistance.
  • Further research is needed to overcome limitations and enhance the efficacy of antiangiogenic treatments.

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